scholarly journals Cryptic indole hydroxylation by a non-canonical terpenoid cyclase parallels bacterial xenobiotic detoxification

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Susann Kugel ◽  
Martin Baunach ◽  
Philipp Baer ◽  
Mie Ishida-Ito ◽  
Srividhya Sundaram ◽  
...  
Keyword(s):  
Xenobiotic Detoxification ◽  
Terpenoid Cyclase

scholarly journals Association of Environmental Arsenic Exposure, Genetic Polymorphisms of Susceptible Genes, and Skin Cancers in Taiwan

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Ling-I Hsu ◽  
Meei-Maan Wu ◽  
Yuan-Hung Wang ◽  
Cheng-Yeh Lee ◽  
Tse-Yen Yang ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Cancer Risk ◽  
Arsenic Exposure ◽  
Skin Carcinogenesis ◽  
Glutathione S Transferase ◽  
Xenobiotic Detoxification ◽  
Skin Cancer Risk ◽  
Metabolic Genes ◽  
Skin Cancers ◽  
And Gender

Deficiency in the capability of xenobiotic detoxification and arsenic methylation may be correlated with individual susceptibility to arsenic-related skin cancers. We hypothesized that glutathione S-transferase (GST M1, T1, and P1), reactive oxygen species (ROS) related metabolic genes (NQO1, EPHX1, and HO-1), and DNA repair genes (XRCC1, XPD, hOGG1, and ATM) together may play a role in arsenic-induced skin carcinogenesis. We conducted a case-control study consisting of 70 pathologically confirmed skin cancer patients and 210 age and gender matched participants with genotyping of 12 selected polymorphisms. The skin cancer risks were estimated by odds ratio (OR) and 95% confidence interval (CI) using logistic regression. EPHX1 Tyr113His, XPD C156A, and GSTT1 null genotypes were associated with skin cancer risk (OR = 2.99, 95% CI = 1.01–8.83; OR = 2.04, 95% CI = 0.99–4.27; OR = 1.74, 95% CI = 1.00–3.02, resp.). However, none of these polymorphisms showed significant association after considering arsenic exposure status. Individuals carrying three risk polymorphisms of EPHX1 Tyr113His, XPD C156A, and GSTs presented a 400% increased skin cancer risk when compared to those with less than or equal to one polymorphism. In conclusion, GSTs, EPHX1, and XPD are potential genetic factors for arsenic-induced skin cancers. The roles of these genes for arsenic-induced skin carcinogenesis need to be further evaluated.

scholarly journals The genetic paradigms of dietary restriction fail to extend life span in cep-1(gk138) mutant of C. elegans p53 due to possible background mutations

2020 ◽  
Author(s):  
Anita Goyala ◽  
Aiswarya Baruah ◽  
Arnab Mukhopadhyay
Keyword(s):  
Life Span ◽  
Dietary Restriction ◽  
Model Systems ◽  
Regulation Of Expression ◽  
Life Span Extension ◽  
Phenotypic Differences ◽  
C Elegans ◽  
Xenobiotic Detoxification ◽  
Organismal Biology ◽  
Extend Life Span

AbstractDietary restriction (DR) increases life span and improves health in most model systems tested, including non-human primates. In C. elegans, as in other models, DR leads to reprogramming of metabolism, improvements in mitochondrial health, large changes in gene expression, including increase in expression of cytoprotective genes, better proteostasis etc. Understandably, multiple global transcriptional regulators like transcription factors FOXO/DAF-16, FOXA/PHA-4, HSF1/HSF-1 and NRF2/SKN-1 are important for DR longevity. Considering the wide-ranging effects of p53 on organismal biology, we asked whether the C. elegans ortholog, CEP-1 is required for DR-mediated longevity assurance. We employed the widely-used TJ1 strain of cep-1(gk138). We show that cep-1(gk138) suppresses the life span extension of two genetic paradigms of DR, but two non-genetic modes of DR remain unaffected in this strain. We find that in cep-1(gk138), two aspects of DR, increased autophagy and the up-regulation of expression of cytoprotective xenobiotic detoxification program (cXDP) genes are dampened. Importantly, we find that background mutation(s) in the strain may be the actual cause for the phenotypic differences that we observed and cep-1 may not be directly involved in genetic DR-mediated longevity assurance in worms. Identifying these mutation(s) may reveal a novel regulator of longevity required specifically by genetic modes of DR.

scholarly journals Transcriptional Regulation of Xenobiotic Detoxification in Drosophila

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Jyoti Ranjan Misra ◽  
Michael A Horner ◽  
Geanette Lam ◽  
Carl S Thummel
Keyword(s):  
Transcriptional Regulation ◽  
Xenobiotic Detoxification

scholarly journals Growth hormone-releasing hormone disruption extends lifespan and regulates response to caloric restriction in mice

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Liou Y Sun ◽  
Adam Spong ◽  
William R Swindell ◽  
Yimin Fang ◽  
Cristal Hill ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Caloric Restriction ◽  
Stress Resistance ◽  
Growth Hormone Releasing Hormone ◽  
Somatotropic Axis ◽  
Releasing Hormone ◽  
Xenobiotic Detoxification ◽  
Expression Of Genes ◽  
Extended Longevity ◽  
The Impact

We examine the impact of targeted disruption of growth hormone-releasing hormone (GHRH) in mice on longevity and the putative mechanisms of delayed aging. GHRH knockout mice are remarkably long-lived, exhibiting major shifts in the expression of genes related to xenobiotic detoxification, stress resistance, and insulin signaling. These mutant mice also have increased adiponectin levels and alterations in glucose homeostasis consistent with the removal of the counter-insulin effects of growth hormone. While these effects overlap with those of caloric restriction, we show that the effects of caloric restriction (CR) and the GHRH mutation are additive, with lifespan of GHRH-KO mutants further increased by CR. We conclude that GHRH-KO mice feature perturbations in a network of signaling pathways related to stress resistance, metabolic control and inflammation, and therefore provide a new model that can be used to explore links between GHRH repression, downregulation of the somatotropic axis, and extended longevity.

scholarly journals Molecular Cloning and Characterization of Five Glutathione S-Transferase Genes and Promoters from Micromelalopha troglodyta (Graeser) (Lepidoptera: Notodontidae) and Their Response to Tannic Acid Stress

Insects ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 339
Author(s):  
Fang Tang ◽  
Huizhen Tu ◽  
Qingli Shang ◽  
Xiwu Gao ◽  
Pei Liang
Keyword(s):  
Mrna Expression ◽  
Tannic Acid ◽  
Quantitative Polymerase Chain Reaction ◽  
Acid Stress ◽  
Glutathione S Transferase ◽  
Promoter Sequences ◽  
Xenobiotic Detoxification ◽  
Regulatory Cascade ◽  
Glutathione S Transferases ◽  
Fat Bodies

Plants accumulate phenolic compounds such as tannic acid to resist insect herbivores. The survival of insects exposed to toxic secondary metabolites depends on the detoxification metabolism mediated by limited groups of glutathione S-transferases (GSTs). Micromelalopha troglodyta (Graeser) (Lepidoptera: Notodontidae) is an important foliar pest of poplar trees. GSTs play an important role in xenobiotic detoxification in M. troglodyta. Five GST genes were identified in M. troglodyta and were classified into five different cytosolic GST classes, delta, omega, sigma, theta, and zeta. Real-time fluorescent quantitative polymerase chain reaction (qPCR) was used to determine the mRNA expression of the five cloned GSTs in the midguts and fat bodies of M. troglodyta. The mRNA expression of the five GSTs was significantly induced when M. troglodyta was exposed to tannic acid. To further understand the tannic acid regulatory cascade, the 5′-flanking promoter sequences of the five MtGSTs were isolated by genome walking methods, and the promoters were very active and induced by tannic acid. In summary, the induction of GST mRNA expression was due to the response of five MtGST promoters to tannic acid. Therefore, MtGST promoters play an important role in the regulation of GST transcription.

scholarly journals The Nuclear Receptor Seven Up Regulates Genes Involved in Immunity and Xenobiotic Response in the Adult Drosophila Female Fat Body

2020 ◽  
Vol 10 (12) ◽  
pp. 4625-4635
Author(s):  
Lesley N. Weaver ◽  
Daniela Drummond-Barbosa
Keyword(s):  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Adult Female ◽  
Fat Body ◽  
Peripheral Tissues ◽  
Immune Genes ◽  
Xenobiotic Detoxification ◽  
Intrinsic Roles ◽  
Xenobiotic Response ◽  
Adult Drosophila

The physiology of organisms depends on inter-organ communication in response to changes in the environment. Nuclear receptors are broadly expressed transcription factors that respond to circulating molecules to control many biological processes, including immunity, detoxification, and reproduction. Although the tissue-intrinsic roles of nuclear receptors in reproduction have been extensively studied, there is increasing evidence that nuclear receptor signaling in peripheral tissues can also influence oogenesis. We previously showed that the Drosophila nuclear receptor Seven up (Svp) is required in the adult fat body to regulate distinct steps of oogenesis; however, the relevant downstream targets of Svp remain unknown. Here, we took an RNA sequencing approach to identify candidate Svp targets specifically in the adult female fat body that might mediate this response. svp knockdown in the adult female fat body significantly downregulated immune genes involved in the first line of pathogen defense, suggesting a role for Svp in stimulating early immunity. In addition, we found that Svp transcriptionally regulates genes involved in each step of the xenobiotic detoxification response. Based on these findings, we propose a testable model in which Svp functions in the adult female fat body to stimulate early defense against pathogens and facilitate detoxification as part of its mechanisms to promote oogenesis.

scholarly journals Multi-domain terpenoid cyclase architecture and prospects for proximity in bifunctional catalysis

2016 ◽  
Vol 41 ◽  
pp. 27-37 ◽  
Author(s):  
Mengbin Chen ◽  
Golda G Harris ◽  
Travis A Pemberton ◽  
David W Christianson
Keyword(s):  
Bifunctional Catalysis ◽  
Terpenoid Cyclase
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